Transcriptional activation of short interspersed elements by DNA-damaging agents

Short interspersed elements (SINEs), typified by the human Alu repeat, are RNA polymerase III (pol III)-transcribed sequences that replicate within th e genome through an RNA intermediate. Replication of SINEs has been extensi ve in mammalian evolution: an estimated 5% of the human genome consists of Alu repeats. The mechanisms regulating transcription, reverse transcription , and reinsertion of SINE elements in genomic DNA are poorly understood. He re we report that expression of murine SINE transcripts of both the B1 and B2 classes is strongly upregulated after prolonged exposure to cisplatin, e toposide, or gamma radiation. A similar induction of Alu transcripts in hum an cells occurs under these conditions. This induction is not due to a gene ral upregulation of pol III activity in either species. Genotoxic treatment of murine cells containing an exogenous human Alu element induced Alu tran scription. Concomitant with the increased expression of SINEs, an increase in cellular reverse transcriptase was observed after exposure to these same DNA-damaging agents. These findings suggest that genomic damage may be an important activator of SINEs, and that SINE mobility may contribute to seco ndary malignancy after exposure to DNA-damaging chemotherapy. (C) 2001 Wile y-Liss, Inc.